How do you interpret antibiotic susceptibility test results?

How to Interpret Antibiotic Susceptibility Test Results

Interpret antibiotic susceptibility tests by categorizing bacteria into three clinical categories—Susceptible (S), Intermediate (I), or Resistant (R)—based on standardized breakpoint values (MIC or zone diameter), then select antibiotics accordingly: use standard-dose therapy for susceptible organisms, consider higher doses or alternative agents for intermediate results, and avoid resistant antibiotics entirely. 1

Understanding the Three Clinical Categories

Susceptible (S)

• Bacteria classified as susceptible are likely to respond to treatment with standard recommended dosages of the antibiotic. 1
• These organisms either lack resistance mechanisms entirely or possess only low-level resistance mechanisms that do not significantly affect clinical outcomes. 2, 1
• Treatment with standard doses is expected to be effective, and these antibiotics should be your first-line choice. 1

Intermediate (I)

• Intermediate bacteria show variable or indeterminate responses to standard antibiotic therapy but may still be effectively treated if the antibiotic concentrates at the infection site or if higher dosages can be safely administered. 2, 1
• This category serves as a technical buffer zone that prevents small laboratory variations from causing major interpretation errors. 2
• The intermediate designation also indicates possible clinical applicability in body sites where the drug physiologically concentrates (e.g., urinary tract, bile) or where high dosages can be used safely. 3
• Treat intermediate results with caution: consider using maximum tolerated doses, alternative antibiotics, or agents that concentrate at the infection site. 1

Resistant (R)

• Resistant bacteria are unlikely to respond even to maximum doses of the antibiotic and possess specific resistance mechanisms demonstrated phenotypically or genotypically. 2, 1
• Clinical resistance occurs when infection is highly unlikely to respond to therapy, though many factors beyond in vitro testing affect actual treatment response. 2
• Do not use antibiotics to which the organism is resistant; select alternative therapy immediately. 3

Technical Interpretation: Understanding MIC and Breakpoints

Minimum Inhibitory Concentration (MIC)

• The MIC is the lowest concentration (expressed in mg/L) that prevents bacterial growth under defined laboratory conditions. 2
• MIC values are determined through standardized dilution methods (broth dilution, agar dilution, or gradient diffusion) using controlled inoculum concentrations and growth conditions. 4
• These values provide quantitative estimates of bacterial susceptibility to antimicrobial compounds. 3

Breakpoints

• Breakpoints are specific MIC values or inhibition zone diameters used to assign bacteria to the clinical categories of susceptible, intermediate, or resistant. 2
• These values are based on achievable antibiotic concentrations at infection sites (or in blood as a practical approximation), pharmacokinetics, and correlation with clinical outcomes. 2, 4
• Pay careful attention to breakpoint symbols: "≤" means "equal to or less than," while "≥" means "equal to or greater than." 2

Critical Clinical Considerations

The In Vitro vs. In Vivo Disconnect

• Laboratory resistance does not always predict clinical failure, creating a critical gap between susceptibility data and actual patient outcomes. 5
• Bacteria with low-level microbiological resistance mechanisms may still be clinically susceptible (sometimes called "borderline susceptible"). 2, 5
• MIC breakpoints must be interpreted relative to antibiotic concentrations achievable at the specific infection site, not just blood levels. 5
• For example, β-lactams can eradicate "nonsusceptible" pneumococcal strains from lungs because achievable tissue concentrations exceed MIC breakpoints. 5

When Susceptibility Testing is Indicated

• Perform susceptibility testing only for pathogens contributing to an infectious process that warrants antimicrobial therapy when susceptibility cannot be reliably predicted from organism identity alone. 6
• Testing is most valuable for organisms capable of demonstrating resistance to commonly prescribed antibiotics. 6
• Do not perform testing on predictably susceptible organisms (e.g., Streptococcus pyogenes to penicillin) or on mixed growth/normal flora where isolates bear little relationship to the actual infection. 6

Adjusting Therapy Based on Results

• If the patient is clinically improving on empirical therapy, there may be no reason to change antibiotics even if isolated organisms show in vitro resistance to the prescribed agent. 7
• Conversely, if clinical response is inadequate, adjust antimicrobial choice based on susceptibility results. 7
• Consider patient-specific factors including previous antibiotic exposure, hospitalization history, and recurrent infections, which increase likelihood of resistant organisms. 7

Common Pitfalls and How to Avoid Them

Misinterpreting Intermediate Results

• Do not treat intermediate results as equivalent to resistant—these organisms may still respond with dose optimization or site-specific concentration. 2, 1
• Consider the infection site: urinary tract infections may respond to intermediate organisms because many antibiotics concentrate highly in urine. 7

Ignoring Clinical Context

• Never rely solely on susceptibility data without considering the clinical presentation, infection site, and patient factors. 7
• Resistance patterns vary based on previous antibiotic therapy, hospitalization, and recurrent infections. 7

Overinterpreting Mixed or Contaminated Cultures

• Susceptibility testing on mixed growth or normal flora is dangerously misleading and should not guide therapy. 6
• Ensure proper specimen collection before initiating antimicrobials to obtain meaningful culture results. 7

Cross-Resistance Patterns

• Recognize that resistance to one antibiotic may predict resistance to others in the same chemical class (e.g., β-lactams, aminoglycosides, macrolides). 2
• Some resistance mechanisms (impermeability, efflux pumps) affect multiple antibiotic classes—this is called "associated resistance." 2

Practical Application Algorithm

1. Obtain culture before starting antibiotics whenever possible. 7
2. Start empirical therapy based on likely pathogens and local resistance patterns.
3. When susceptibility results return, categorize each organism as S, I, or R for tested antibiotics. 1
4. If the organism is susceptible (S) to current therapy and patient is improving, continue current antibiotic. 7
5. If the organism is intermediate (I), assess whether higher doses are safe or if the infection site allows drug concentration (e.g., urinary tract). 1
6. If the organism is resistant (R) or patient is not improving, switch to an antibiotic showing susceptibility. 3
7. Consider narrowing spectrum when possible to target only isolated pathogens. 7